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Potential transmission chains of variant B.1.1.7 and co-mutations of SARS-CoV-2
Jingsong Zhang; Yang Zhang; Junyan Kang; Shuiye Chen; Yongqun He; Benhao Han; Mofang Liu; Lina Lu; Li Li; Zhigang Yi; Luonan Chen.
  • Jingsong Zhang; Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China
  • Yang Zhang; Shanghai Medical College, Fudan University, Shanghai 200032, China
  • Junyan Kang; Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China
  • Shuiye Chen; School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China
  • Yongqun He; University of Michigan Medical School, Ann Arbor, MI 48109, USA
  • Benhao Han; Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China
  • Mofang Liu; Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China
  • Lina Lu; Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China
  • Li Li; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
  • Zhigang Yi; Fudan University
  • Luonan Chen; Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China
Preprint in English | bioRxiv | ID: ppbiorxiv-440141
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ABSTRACT
The presence of SARS-CoV-2 mutants, including the emerging variant B.1.1.7, has raised great concerns in terms of pathogenesis, transmission, and immune escape. Characterizing SARS-CoV-2 mutations, evolution, and effects on infectivity and pathogenicity is crucial to the design of antibody therapies and surveillance strategies. Here we analyzed 454,443 SARS-CoV-2 spike genes/proteins and 14,427 whole-genome sequences. We demonstrated that the early variant B.1.1.7 may not have evolved spontaneously in the United Kingdom or within human populations. Our extensive analyses suggested that Canidae, Mustelidae or Felidae, especially the Canidae family (for example, dog) could be a possible host of the direct progenitor of variant B.1.1.7. An alternative hypothesis is that the variant was simply yet to be sampled. Notably, the SARS-CoV-2 whole genome represents a large number of potential co-mutations with very strong statistical significances (p valueSARS-CoV-2 reporter replicon system to introduce the dominant co-mutations NSP12_c14408t, 5UTR_c241t, and NSP3_c3037t into the viral genome, and to monitor the effect of the mutations on viral replication. Our experimental results demonstrated that the co-mutations significantly attenuated the viral replication. The study provides valuable clues for discovering the transmission chains of variant B.1.1.7 and understanding the evolutionary process of SARS-CoV-2.
Full text: Available Collection: Preprints Database: bioRxiv Topics: Variants Language: English Year: 2021 Document Type: Preprint

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Full text: Available Collection: Preprints Database: bioRxiv Topics: Variants Language: English Year: 2021 Document Type: Preprint